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Inhibition of Osteoclastogenesis and Bone Resorption in vitro and in vivo by a prenylflavonoid xanthohumol from hops.

Li J, Zeng L, Xie J, Yue Z, Deng H, Ma X, Zheng C, Wu X, Luo J, Liu M - Sci Rep (2015)

Bottom Line: In this study, we examined the effects of xanthohumol (XN), an abundant prenylflavonoid from hops plant, on osteoclastogenesis, osteoclast resorption, and RANKL-induced signaling pathway using both in vitro and in vivo assay systems.At the molecular level, XN disrupted the association of RANK and TRAF6, resulted in the inhibition of NF-κB and Ca(2+)/NFATc1 signaling pathway during osteoclastogenesis.As a results, XN suppressed the expression of osteoclastogenesis-related marker genes, including CtsK, Nfatc1, Trap, Ctr.

View Article: PubMed Central - PubMed

Affiliation: Shanghai Fengxian District Central Hospital and East China Normal University Joint Center for Translational Medicine, Shanghai Key laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.

ABSTRACT
Excessive RANKL signaling leads to superfluous osteoclast formation and bone resorption, is widespread in the pathologic bone loss and destruction. Therefore, targeting RANKL or its signaling pathway has been a promising and successful strategy for this osteoclast-related diseases. In this study, we examined the effects of xanthohumol (XN), an abundant prenylflavonoid from hops plant, on osteoclastogenesis, osteoclast resorption, and RANKL-induced signaling pathway using both in vitro and in vivo assay systems. In mouse and human, XN inhibited osteoclast differentiation and osteoclast formation at the early stage. Furthermore, XN inhibited osteoclast actin-ring formation and bone resorption in a dose-dependent manner. In ovariectomized-induced bone loss mouse model and RANKL-injection-induced bone resorption model, we found that administration of XN markedly inhibited bone loss and resorption by suppressing osteoclast activity. At the molecular level, XN disrupted the association of RANK and TRAF6, resulted in the inhibition of NF-κB and Ca(2+)/NFATc1 signaling pathway during osteoclastogenesis. As a results, XN suppressed the expression of osteoclastogenesis-related marker genes, including CtsK, Nfatc1, Trap, Ctr. Therefore, our data demonstrated that XN inhibits osteoclastogenesis and bone resorption through RANK/TRAF6 signaling pathways. XN could be a promising drug candidate in the treatment of osteoclast-related diseases such as postmenopausal osteoporosis.

No MeSH data available.


Related in: MedlinePlus

XN inhibits RANKL-induced actin-ring formation and bone resorption.(A) The effect of XN on actin-ring formation of osteoclast. Mouse BMMs were incubated with RANKL (30 ng/ml) in the presence of M-CSF (20 ng/ml), followed by treatment with indicated doses of XN. Cells were fixed and stained for F-actin (top). Osteoclasts with actin-rings were counted (bottom). (B) The effect of XN on pits formation of osteoclast. Mouse BMMs were cultured with M-CSF (20 ng/ml) and RANKL (30 ng/ml) for 6 days with or without indicated doses of XN. The cells were washed and the resorption pits were stained with Mayer’s hematoxylin and photographed (top, original magnification, ×40). The numbers of pits were analyzed with Image-Pro software (bottom). Column, means of experiments performed in triplicate; bar, SD.
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f2: XN inhibits RANKL-induced actin-ring formation and bone resorption.(A) The effect of XN on actin-ring formation of osteoclast. Mouse BMMs were incubated with RANKL (30 ng/ml) in the presence of M-CSF (20 ng/ml), followed by treatment with indicated doses of XN. Cells were fixed and stained for F-actin (top). Osteoclasts with actin-rings were counted (bottom). (B) The effect of XN on pits formation of osteoclast. Mouse BMMs were cultured with M-CSF (20 ng/ml) and RANKL (30 ng/ml) for 6 days with or without indicated doses of XN. The cells were washed and the resorption pits were stained with Mayer’s hematoxylin and photographed (top, original magnification, ×40). The numbers of pits were analyzed with Image-Pro software (bottom). Column, means of experiments performed in triplicate; bar, SD.

Mentions: To further examine the effects of XN on osteoclastogenesis, we examined whether XN affected RANKL-induced osteoclast function by bone resorption assays. Firstly, we tested whether XN could affect the actin-ring formation, which is a prerequisite for osteoclast bone resorption and is the most obvious character of mature osteoclast during osteoclastogenesis618. In the presence of RANKL exposure, BMMs can differentiate into mature osteoclasts and form distinct actin-ring structures (Fig. 2A, left). However, XN significantly reduced the size and the number of actin-ring structures in a dose-dependent manner, suggesting that XN suppressed the formation of actin-rings by matured osteoclasts.


Inhibition of Osteoclastogenesis and Bone Resorption in vitro and in vivo by a prenylflavonoid xanthohumol from hops.

Li J, Zeng L, Xie J, Yue Z, Deng H, Ma X, Zheng C, Wu X, Luo J, Liu M - Sci Rep (2015)

XN inhibits RANKL-induced actin-ring formation and bone resorption.(A) The effect of XN on actin-ring formation of osteoclast. Mouse BMMs were incubated with RANKL (30 ng/ml) in the presence of M-CSF (20 ng/ml), followed by treatment with indicated doses of XN. Cells were fixed and stained for F-actin (top). Osteoclasts with actin-rings were counted (bottom). (B) The effect of XN on pits formation of osteoclast. Mouse BMMs were cultured with M-CSF (20 ng/ml) and RANKL (30 ng/ml) for 6 days with or without indicated doses of XN. The cells were washed and the resorption pits were stained with Mayer’s hematoxylin and photographed (top, original magnification, ×40). The numbers of pits were analyzed with Image-Pro software (bottom). Column, means of experiments performed in triplicate; bar, SD.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4664947&req=5

f2: XN inhibits RANKL-induced actin-ring formation and bone resorption.(A) The effect of XN on actin-ring formation of osteoclast. Mouse BMMs were incubated with RANKL (30 ng/ml) in the presence of M-CSF (20 ng/ml), followed by treatment with indicated doses of XN. Cells were fixed and stained for F-actin (top). Osteoclasts with actin-rings were counted (bottom). (B) The effect of XN on pits formation of osteoclast. Mouse BMMs were cultured with M-CSF (20 ng/ml) and RANKL (30 ng/ml) for 6 days with or without indicated doses of XN. The cells were washed and the resorption pits were stained with Mayer’s hematoxylin and photographed (top, original magnification, ×40). The numbers of pits were analyzed with Image-Pro software (bottom). Column, means of experiments performed in triplicate; bar, SD.
Mentions: To further examine the effects of XN on osteoclastogenesis, we examined whether XN affected RANKL-induced osteoclast function by bone resorption assays. Firstly, we tested whether XN could affect the actin-ring formation, which is a prerequisite for osteoclast bone resorption and is the most obvious character of mature osteoclast during osteoclastogenesis618. In the presence of RANKL exposure, BMMs can differentiate into mature osteoclasts and form distinct actin-ring structures (Fig. 2A, left). However, XN significantly reduced the size and the number of actin-ring structures in a dose-dependent manner, suggesting that XN suppressed the formation of actin-rings by matured osteoclasts.

Bottom Line: In this study, we examined the effects of xanthohumol (XN), an abundant prenylflavonoid from hops plant, on osteoclastogenesis, osteoclast resorption, and RANKL-induced signaling pathway using both in vitro and in vivo assay systems.At the molecular level, XN disrupted the association of RANK and TRAF6, resulted in the inhibition of NF-κB and Ca(2+)/NFATc1 signaling pathway during osteoclastogenesis.As a results, XN suppressed the expression of osteoclastogenesis-related marker genes, including CtsK, Nfatc1, Trap, Ctr.

View Article: PubMed Central - PubMed

Affiliation: Shanghai Fengxian District Central Hospital and East China Normal University Joint Center for Translational Medicine, Shanghai Key laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.

ABSTRACT
Excessive RANKL signaling leads to superfluous osteoclast formation and bone resorption, is widespread in the pathologic bone loss and destruction. Therefore, targeting RANKL or its signaling pathway has been a promising and successful strategy for this osteoclast-related diseases. In this study, we examined the effects of xanthohumol (XN), an abundant prenylflavonoid from hops plant, on osteoclastogenesis, osteoclast resorption, and RANKL-induced signaling pathway using both in vitro and in vivo assay systems. In mouse and human, XN inhibited osteoclast differentiation and osteoclast formation at the early stage. Furthermore, XN inhibited osteoclast actin-ring formation and bone resorption in a dose-dependent manner. In ovariectomized-induced bone loss mouse model and RANKL-injection-induced bone resorption model, we found that administration of XN markedly inhibited bone loss and resorption by suppressing osteoclast activity. At the molecular level, XN disrupted the association of RANK and TRAF6, resulted in the inhibition of NF-κB and Ca(2+)/NFATc1 signaling pathway during osteoclastogenesis. As a results, XN suppressed the expression of osteoclastogenesis-related marker genes, including CtsK, Nfatc1, Trap, Ctr. Therefore, our data demonstrated that XN inhibits osteoclastogenesis and bone resorption through RANK/TRAF6 signaling pathways. XN could be a promising drug candidate in the treatment of osteoclast-related diseases such as postmenopausal osteoporosis.

No MeSH data available.


Related in: MedlinePlus